Pharmacological investigation of selected 1,2,4 triazole derivative against ethanol induced gastric ulcer.

Abstract

The present study aims to assess the therapeutic potential of (2S,3S,4S,5S,6S-2-(acetoxymethyl)-6-(4-chlorophenyl)-3-(pyridine-4-yl)5-thioxo-4,5-dihydro-1,2,4-triazol-1-yl tetrahydro-2H-pyran 3,4,5tryltriacetate (JAK05) on gastric ulcer. The current study was designed to evaluate the anti-ulcer potential of JAK05 against ethanol-induced gastric ulcer by employing in silico, in vitro and in vivo techniques. In silico studies, JAK05 has a binding score ranging from -8.51 to -21.38 (kcal/mol). Molecular dynamics simulation at 100 ns shows better structural stability, stable binding affinity and stable conformation when bonded to H⁺/K⁺-ATPase. In vitro study demonstrates that JAK05 inhibits Helicobactor pylori. In vivo study confirmed that JAK05 promotes ulcer healing in rats at a dose of 40 mg/kg and demonstrated a protective effect on the gastric mucosa, comparable to omeprazole by modulating acid secretion and fluid volume. Glutathione, glutathione-s-transferase and catalase levels increased in rat stomach tissue while nitric oxide decreased with the administration of JAK05. Additionally, lipid peroxide levels were found to have significantly decreased. Pathological histopathology analysis shows improved tissue structure and reduced inflammatory markers. These findings were confirmed using immunohistochemistry and enzyme-linked immunosorbent assay. JAK05 exhibits a high affinity for selected targets. JAK05 shows anti-ulcer properties by targeting through multiple mechanisms inhibiting H. pylori, reducing oxidative stress, suppressing inflammation and blocking acid production.